Recent evidence from a diverse array of experimental manipulations implicates brain dopamine neurotransmission in the mediation of intracranial self-stimulation. Evaluation of a dopaminergic substrate for reinforcement, however, presents unusual experimental difficulties in that dopamine is an important mediator of operant behavior and correspondingly, because, by definition, a reinforcer is a behavioral contingency which alters operant response rate. This dilemma was approached experimentally in this project by depleting dopamine unilaterally but having reinforcement delivered from electrodes in both the ipsilateral and contralateral hemispheres. Since the response requirement to obtain reinforcement is the same for both electrodes reinforcement versus motoric effects could be distinguished by the degree to which lesion effects are laterized. Using this paradigm the effects of unilateral 6-hydroxydopamine injections into the substantia nigra on self-stimulation in rats are studied for up to two months postoperatively. Six-hydroxydopamine injections which produce a virtual complete loss of forebrain dopamine initially have a marked bilateral disruptive effect on self-stimulation. The recovery functions for the two hemispheres, however, are different. Self-stimulation in the intact hemisphere recovers completely by four weeks postoperative, whereas self-stimulation obtained from the dopamine deficient hemisphere remains attenuated particularly for high response rates. Thus, dopamine can have effects on self-stimulation related to both motoric and non-motoric dysfunctions.